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At least 37 records · Page 2Linked to original sources

Disulfiram implantation. A placebo-controlled trial with two-year follow-up.

Ten alcoholics implanted with disulfiram had longer periods of abstinence after treatment than did 10 alcoholics implanted with placebo; 7 of the disulfiram-implanted patients experienced a disulfiram-ethanol reaction in uncontrolled drinking situations, while none of the placebo-implanted patients did.

Adult

Sustained release of alcohol: subcutaneous silastic implants in mice.

A sustained-release device for use in ethanol dependence studies in mice is described. The Silastic device, dubbed SERT (sustained ethanol release tube), holds 0.35 milliliter of 95 percent ethanol (by volume) and is implanted under the skin of the back where it releases ethanol for up to 12 hours, with no observable tissue damage. The device may be adaptable to the release of other volatile liquids or drugs, in other animals.

Alcoholic Intoxication

Ventilatory depression in naive and tolerant rats in relation to plasma morphine concentration.

1 The disappearance of morphine from specially formulated pellets containing 75 mg morphine base was measured for 10 days after they were implanted into adult rats; the morphine content decreased at a rate of 5 mg pellet daily.2 From the 2nd to the 6th day of implantation the plasma morphine concentration increased but by the 10th day had declined to only one half the concentration found on day 6.3 Six and 24 h after the pellets were removed from 6 day implanted animals the plasma concentration of morphine amounted to only one quarter to one sixth of the amount in the plasma, respectively, of animals with pellets intact.4 The pulmonary minute volume of naive and implanted rats was depressed by morphine in proportion to the plasma morphine concentration. Less depression was produced by intravenous morphine in the implanted rats than in the naive animals; the greater morphine tolerance displayed by the implanted animals could be shown by the third day of implantation and appeared to be maintained to the 10th day.5 The pulmonary minute volume of implanted rats on the 6th day was much less than the pulmonary minute volume of naive rats. Six and 24 h after the pellets were removed the pulmonary minute volume increased as the plasma morphine concentration decreased.6 The effects on the pulmonary minute volume produced by the slow release of morphine from the implanted pellets was not changed by the development of tolerance while the effects of morphine produced by rapid injection were diminished by the development of tolerance; the different effects of morphine are accordingly linked to the mode of administration.7 We conclude that the action of morphine on the pulmonary minute volume in tolerant rats following rapid injection is fundamentally different from its action following its slow release from implanted pellets, possibly due to differences in access to an undefined neuronal site.

Animals

Antidiuretic effect of morphine in the rat: tolerance and physical dependence.

1 Injection of rats with morphine or methadone, before they received a water load equivalent to 5% of their body weight, produced a dose-dependent antidiuretic effect. Following the antidiuresis, urine was eliminated with kinetics similar to control untreated rats. 2 The antidiuretic effect of morphine or methadone was blocked by naloxone administered before the opiate, or reversed when given after the opiate. 3 Rats implanted with morphine pellets developed a marked degree of tolerance to the antidiuretic effect of morphine. Tolerance was also obtained on injection of three daily doses of morphine or methadone over two days. 4 Withdrawal symptoms were precipitated by naloxone in rats implanted with pellets of morphine; under these conditions the animals showed a marked reduction in urine production as compared to naive rats.

Animals

Treatment of solid Gardner lymphosarcoma with methotrexate sorbed on 2-hydroxyethylmethacrylate polymer in combination with leukovorin.

Implantation of 2-hydroxyethylmethacrylate microporous carrier with sorbed methotrexate (Hema-Hex-MTX) proved more toxic on C3H strain mice with a solid Gardner lymphosarcoma than on tumor-free mice of the same strain. If, during the first week of the experimental disease, the Hema-Hex-MTX implantation was followed by administration of leukovorin in course of next 24 hours the toxicity of MTX was abolished and the treated mice survived significantly longer than control animals.

Animals

The synthesis rate and turnover time of 5-hydroxy-tryptamine in brains of rats treated chronically with morphine.

1. Four schedules of subcutaneous pellet implantation were used to induce tolerance to and physical dependence on morphine in Sprague-Dawley rats. 2. The schedules included implantation of four morphine pellets (each containing 75 mg of morphine free base) during a 3 day period (schedule 1); six pellets during 3 days (schedule 2); six pellets during 7 days (schedule 3) and ten pellets during a 10 day period (schedule 4). 3. A high degree of tolerance and dependence on morphine, comparable to that induced in mouse by implantation of a single morphine pellet for 3 days, was produced with schedule 4. 4. Brain 5-hydroxytryptamine (5-HT) turnover rates as measured by rate of accumulation of 5-HT after monoamine oxidase inhibition by pargyline were not different in rats rendered tolerant to and dependent on morphine according to schedules 1 to 4 when compared with corresponding placebo pellet-implanted rats. 5. The turnover rates of 5-HT in brain of morphine-and placebo pellet-implanted rats (schedule 4) from which the pellets had been removed for 24 h were also similar. 6. It is concluded that tolerance to, and physical dependence upon morphine in the rat is not associated with changes in brain 5-HT dynamics.

Animals

Tolerance to nitrous oxide analgesia in rats and mice.

The purpose of these experiments was to characterize the nature of tolerance to the analgesic action of nitrous oxide. Analgesia was assessed in rats using a tail-flick latency test and in mice using an abdominal constriction test. Rats and mice were exposed to nitrous oxide, 75 per cent, the balance oxygen, continuously for 16--18 hours. On re-exposure to nitrous oxide 30 min later, these animals were found tolerant to nitrous oxide in that the analgesic response was decreased by at least 50 per cent. Animals tolerant to nitrous oxide were not tolerant to morphine. Morphine (0.25--1.5 mg/kg) produced equal degrees of analgesia in control and nitrous oxide-tolerant mice and rats. In contrast, rats made tolerant to morphine by repeated daily injections of as much as 400 mg/kg subcutaneously or by subcutaneous implantation of morphine pellets (75 mg, twice) showed a decreased analgesic response to nitrous oxide. Thus the cross-tolerance between nitrous oxide and morphine appears unique in that it is unidirectional.

Anesthesia, General

The inhibitory effects of presynaptic alpha-adrenoceptor agonists on contractions of guinea-pig ileum and mouse vas deferens in the morphine-dependent and withdrawn states produced in vitro.

1 Isolated ilea from guinea-pigs implanted with morphine pellets were stimulated coaxially, either with or without morphine present in the bath fluid, and the longitudinal contractions recorded. 2 In the absence of morphine the inhibitory effects of the presynaptic alpha-adrenoceptor agonists, clonidine and oxymetazoline were much reduced and the dose-response curve was flat. This state of 'withdrawal' was readily reversed by morphine and levorphanol but not its inactive (+)-isomer, dextrophan. 3 The kappa-agonists, ketazocine and ethylketazocine, also restored the effects of clonidine as did the opioid peptides Tyr-D-Ala-Gly-Phe-D-Leu, acting preferentially on delta-receptors, and Tyr-D-Ala-Gly-MePhe-Met(O)-ol, acting mainly on micro-receptors. 4 The inhibitory effects of adrenaline and adenosine 3',5'-diphosphate were reduced at low but not at high concentrations. 5 In contrast, the inhibitory effect of clonidine on the electrically evoked contractions of vasa deferentia from mice implanted with morphine pellets was not abolished by the lack of morphine in the bath fluid or by addition of naloxone. 6 A possible explanation is suggested for the loss of the inhibitory effects of presynaptic alpha-adrenoceptor agonists in the withdrawn state of the dependent ileum.

Adenosine Diphosphate

Evidence for a rapid in vivo effect on estradiol-17 beta on prolactin secretion in ovariectomized rats.

Repeated intraarterial injections of synthetic thryrotropin releasing hormone (TRH, 1 microgram/rat) increased plasma prolactin levels 4 hours after a single subcutaneous injection of 10 micrograms estradiol-17 beta (E2-17 beta) in rats ovariectomized 1, 2 or 4 weeks and at 2 hours after E2-17 beta injection in rats ovariectomized for 6 weeks. The effect of TRH was still present at 24 but not 48 hours after estradiol treatment. TRH-induced increases in plasma prolactin were similar in groups of rats treated with 10 micrograms E2-17 beta (s.c.) or implanted with 0.5 cm Silastic capsules of crystalline E2-17 beta (s.c.) whereas smaller, yet significant, TRH-induced increases in plasma prolactin were observed in rats injected s.c. with 1.0 microgram E2-17 beta. Single intraarterial injections of TRH at 4 or 8 hours after E2-17 beta treatment induced increases in plasma prolactin similar in magnitude to those observed at the same times after E2-17 beta in rats given repeated TRH injections. No effect of TRH was observed in ovariectomized rats given sesame oil and E2-17 beta treatment did not influence plasma prolactin in rats given saline instead of TRH. Intraarterial administration of serotonin creatinine sulfate (5-HT, 10 mg/kg body weight) induced marked increases in plasma prolactin in rats ovariectomized for 4 weeks which were potentiated at 2 and 6 hours after E2-17 beta (10 micrograms) treatment. The data show that estradiol has a fairly rapid stimulatory effect on plasma levels of prolactin induced by two different secretagogues but the exact site and mechanism of action remain unresolved.

Animals

Steroidal compounds (injectable and implants) affecting spermatogenesis in men.

The effect of androgen and different progestins on spermatogenesis was studied in young men with subfertility, prostatovesiculitis and haematospermia, and in older men with benign hypertrophy of the prostate. The compounds (testosterone, testosterone oenanthate, ethinyl oestradiol, megestrol acetate, ethinyl norgestrienone and Depo-Provera) were administered intramuscularly, orally or as subcutaneous silastic implants.

Adult